The goal of this project is to study the response of the kidney to fractionated radiation and the interaction of this irradiation with common chemotherapeutic agents. Late damage to nonproliferating tissues is a major limiting factor in radiotherapy and the use of combined radiation and chemotherapy is increasing. There is a paucity of information on late tissue damage from fractionated radiotherapy and on the effects of drug-radiation interactions in such tissues. Special Aims are: 1) To study the time-dependence, or the lack thereof, of the radiation tolerance of the kidney; 2) to study the effects of long and short gaps in treatment on the radiation tolerance of the kidney; 3) to determine the age dependence of the radiation tolerance of the kidney; 4) to determine the extent of protection produced by partial kidney shielding during irradiation; 5) to study the effects of chronic administration of common chemotherapeutic agents on the renal toxicity of radiation; 6) to determine the effects of kidney irradiation on the pharmacokinetics of methotrexate. These experiments will simulate in rats the drug-radiation doses and schedules used in man. Radiation and drugs will, therefore, be administered in fractionated doses to unanesthetized animals.